Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000536.4(RAG2):c.1095T>C (p.Ser365=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA5950474

304552 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3454b9e8-3665-4835-8fc9-2cc823ee5ebc

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000536.4:c.1095T>C

NM_000536.4(RAG2):c.1095T>C (p.Ser365=)

NC_000011.10:g.36593074A>G

CM000673.2:g.36593074A>G

NC_000011.9:g.36614624A>G

CM000673.1:g.36614624A>G

NC_000011.8:g.36571200A>G

NG_007573.1:g.10163T>C

NG_033154.1:g.3582A>G

ENST00000311485.8:c.1095T>C

ENST00000311485.7:c.1095T>C

ENST00000524423.1:n.131+5028T>C

ENST00000534663.1:c.*193A>G

ENST00000618712.4:c.1095T>C

NM_000536.3:c.1095T>C

NM_001243785.1:c.1095T>C

NM_001243786.1:c.1095T>C

NM_001243785.2:c.1095T>C

NM_001243786.2:c.1095T>C

Likely Benign

BS1 BP7

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAG2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The NM_000536.4:c.1095T>C variant is a synonymous (silent) variant (p.Ser365=) with no predicted splice impact (BP7). This variant has not been reported in the literature in individuals with RAG2-related conditions. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00314 (79/25120) in the Finnish population, which is higher than the ClinGen SCID VCEP's threshold for BS1 (>0.00195). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive SCID based on the ACMG criteria applied BS1 and BP7, as specified by the ClinGen SCID VCEP (VCEP specifications 1).

BS1

Highest subpopulation frequency (Finnish) in gnomAD is 79/25120 (0.00314) which is greater that the allele frequency expected for RAG2-related disease (>0.00195). There is also 1 homozygote in gnomAD.

BP7

Silent variant, no predicted splice impact. As outlined in SCID VCEP RAG2 specifications, nucleotide conservation is not required in order to apply BP7.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.